Repurposing Anti-Malaria Phytomedicine Artemisinin as a COVID-19 Drug

DOI record: { "DOI": "10.3389/fphar.2021.649532", "ISSN": [ "1663-9812" ], "URL": "http://dx.doi.org/10.3389/fphar.2021.649532", "abstract": "<jats:p>Artemisinin is an anti-inflammatory phytomedicine with broad-spectrum antiviral activity. Artemisinin and its antimalarial properties were discovered by the Chinese scientist Tu Youyu, who became one of the laureates of the 2015 Nobel Prize in Physiology or Medicine for this breakthrough in tropical medicine. It is a commonly used anti-malaria drug. Artemisinin has recently been repurposed as a potential COVID-19 drug. Its documented anti-SARS-CoV-2 activity has been attributed to its ability to inhibit spike-protein mediated and TGF-β-dependent early steps in the infection process as well as its ability to disrupt the post-entry intracellular events of the SARS-CoV-2 infection cycle required for viral replication. In addition, Artemisinin has anti-inflammatory activity and reduces the systemic levels of inflammatory cytokines that contribute to cytokine storm and inflammatory organ injury in high-risk COVID-19 patients. We postulate that Artemisinin may prevent the worsening of the health condition of patients with mild-moderate COVID-19 when administered early in the course of their disease.</jats:p>", "alternative-id": [ "10.3389/fphar.2021.649532" ], "author": [ { "affiliation": [], "family": "Uckun", "given": "Fatih M.", "sequence": "first" }, { "affiliation": [], "family": "Saund", "given": "Saran", "sequence": "additional" }, { "affiliation": [], "family": "Windlass", "given": "Hitesh", "sequence": "additional" }, { "affiliation": [], "family": "Trieu", "given": "Vuong", "sequence": "additional" } ], "container-title": "Frontiers in Pharmacology", "container-title-short": "Front. Pharmacol.", "content-domain": { "crossmark-restriction": true, "domain": [ "frontiersin.org" ] }, "created": { "date-parts": [ [ 2021, 3, 19 ] ], "date-time": "2021-03-19T05:21:51Z", "timestamp": 1616131311000 }, "deposited": { "date-parts": [ [ 2021, 3, 19 ] ], "date-time": "2021-03-19T05:22:06Z", "timestamp": 1616131326000 }, "funder": [ { "DOI": "10.13039/100016631", "doi-asserted-by": "publisher", "id": [ { "asserted-by": "publisher", "id": "10.13039/100016631", "id-type": "DOI" } ], "name": "Mateon Therapeutics" } ], "indexed": { "date-parts": [ [ 2025, 2, 21 ] ], "date-time": "2025-02-21T17:36:07Z", "timestamp": 1740159367975, "version": "3.37.3" }, "is-referenced-by-count": 31, "issued": { "date-parts": [ [ 2021, 3, 19 ] ] }, "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2021, 3, 19 ] ], "date-time": "2021-03-19T00:00:00Z", "timestamp": 1616112000000 } } ], "link": [ { "URL": "https://www.frontiersin.org/articles/10.3389/fphar.2021.649532/full", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1965", "original-title": [], "prefix": "10.3389", "published": { "date-parts": [ [ 2021, 3, 19 ] ] }, "published-online": { "date-parts": [ [ 2021, 3, 19 ] ] }, "publisher": "Frontiers Media SA", "reference": [ { "DOI": "10.1016/s0014-5793(03)00905-0", "article-title": "Artemisinin inhibits inducible nitric oxide synthase and nuclear factor NF-kB activation", "author": "Aldieri", "doi-asserted-by": "publisher", "first-page": "141", "journal-title": "FEBS Lett.", "key": "B1", "volume": "552", "year": "2003" }, { "article-title": "Potential approach for fighting against corona virus disease", "author": "Alhelfawi", "first-page": "127", "journal-title": "ASRJETS", "key": "B2", "volume": "66", "year": "2020" }, { "DOI": "10.1002/(sici)1099-081x(199805)19:4<245::aid-bdd99>3.0.co;2-z", "article-title": "Artemisinin pharmacokinetics in healthy adults after 250, 500 and 1000 mg single oral doses", "author": "Ashton", "doi-asserted-by": "publisher", "first-page": "245", "journal-title": "Biopharm. Drug Dispos", "key": "B3", "volume": "19", "year": "1998" }, { "DOI": "10.1517/14728222.2014.902938", "article-title": "Protein-based therapies for acute lung injury: targeting neutrophil extracellular traps", "author": "Bossman", "doi-asserted-by": "publisher", "first-page": "703", "journal-title": "Expert Opin. Ther. Targets", "key": "B4", "volume": "18", "year": "2014" }, { "DOI": "10.1007/s00134-004-2503-2", "article-title": "Active transforming growth factor-beta1 activates the procollagen I promoter in patients with acute lung injury", "author": "Budinger", "doi-asserted-by": "publisher", "first-page": "121", "journal-title": "Intensive Care Med.", "key": "B5", "volume": "31", "year": "2005" }, { "DOI": "10.1021/acsinfecdis.0c00522", "article-title": "Anti-SARS-CoV-2 potential of artemisinins in vitro", "author": "Cao", "doi-asserted-by": "publisher", "first-page": "2524", "journal-title": "ACS Infect Dis.", "key": "B6", "volume": "6", "year": "2020" }, { "DOI": "10.7150/ijbs.46891", "article-title": "A potential treatment of COVID-19 with TGF-β blockade", "author": "Chen", "doi-asserted-by": "publisher", "first-page": "1954", "journal-title": "International Journal of Biological Sciences", "key": "B7", "volume": "16", "year": "2020" }, { "DOI": "10.1016/j.idcr.2020.e00741", "article-title": "Post-artemisinin delayed hemolysis after oral therapy for P. falciparum infection", "author": "Conlon", "doi-asserted-by": "publisher", "first-page": "e00741", "journal-title": "IDCases", "key": "B8", "volume": "20", "year": "2020" }, { "DOI": "10.3390/Microorganisms8010085", "article-title": "The use of antimalarial drugs against viral infection", "author": "D’alessandro", "doi-asserted-by": "publisher", "first-page": "85", "journal-title": "Microorganisms", "key": "B9", "volume": "8", "year": "2020" }, { "DOI": "10.4269/ajtmh.1997.56.503", "article-title": "The pharmacokinetics of a single dose of artemisinin in patients with uncomplicated falciparum malaria", "author": "De Vries", "doi-asserted-by": "publisher", "first-page": "503", "journal-title": "Am. J. Trop. Med. Hyg.", "key": "B10", "volume": "56", "year": "1997" }, { "DOI": "10.4269/ajtmh.1994.51.785", "article-title": "The pharmacokinetics of a single dose of artemisinin in healthy Vietnamese subjects", "author": "Duc", "doi-asserted-by": "publisher", "first-page": "785", "journal-title": "Am. J. Trop. Med. Hyg.", "key": "B11", "volume": "51", "year": "1994" }, { "DOI": "10.1086/591195", "article-title": "The antiviral activities of artemisinin and artesunate", "author": "Efferth", "doi-asserted-by": "publisher", "first-page": "804", "journal-title": "Clin. Infect Dis.", "key": "B12", "volume": "47", "year": "2008" }, { "DOI": "10.21203/RS.3.RS-25850/V1", "article-title": "Inhibition of COVID-19 RNA-dependent RNA polymerase by natural bioactive compounds: molecular docking analysis", "author": "El-Aziz Abd", "doi-asserted-by": "publisher", "journal-title": "Preprint", "key": "B13", "year": "2020" }, { "DOI": "10.1080/07391102.2020.1761881", "article-title": "Natural products may interfere with SARS-CoV-2 attachment to the host cell", "author": "Elfiky", "doi-asserted-by": "publisher", "journal-title": "J. Biomol. Struct. Dyn", "key": "B14", "year": "2020" }, { "DOI": "10.1001/jama.2020.24243", "article-title": "All-cause excess mortality and COVID-19-related mortality among US adults aged 25-44 Years, March-july 2020", "author": "Faust", "doi-asserted-by": "publisher", "first-page": "785", "journal-title": "JAMA", "key": "B15", "volume": "325", "year": "2021" }, { "DOI": "10.1101/2020.04.06.210.1101/2020.04.06.20050575", "article-title": "Pulmonary and cardiac Pathology in COVID -19: the first autopsy series from New Orleans", "author": "Fox", "doi-asserted-by": "publisher", "journal-title": "medRxiv", "key": "B16", "year": "2020" }, { "DOI": "10.1073/pnas.1322478111", "article-title": "TGF-β and lung fluid balance in ARDS", "author": "Frank", "doi-asserted-by": "publisher", "first-page": "885", "journal-title": "Proc. Natl. Acad. Sci. USA", "key": "B17", "volume": "111", "year": "2014" }, { "article-title": "In vitro efficacy of Artemisinin-based treatments against SARS-CoV-2", "author": "Gilmore", "journal-title": "bioRxiv", "key": "B19", "year": "2020" }, { "DOI": "10.1128/aac.46.4.1026-1031.2002", "article-title": "Artemisinin pharmacokinetics and efficacy in uncomplicated-malaria patients treated with two different dosage regimens", "author": "Gordi", "doi-asserted-by": "publisher", "first-page": "1026", "journal-title": "Antimicrob. Agents Chemother.", "key": "B20", "volume": "46", "year": "2002" }, { "DOI": "10.26434/chemrxiv.12071997", "article-title": "Natural product compounds in Alpinia officinarum and ginger are potent SARS-CoV-2 papain-like protease inhibitors", "author": "Goswami", "doi-asserted-by": "publisher", "journal-title": "chemRxiv", "key": "B21", "year": "2020" }, { "DOI": "10.1080/07391102.2020.1764868", "article-title": "Potential inhibitors of coronavirus 3-chymotrypsin-like protease (3CL pro): an in silico screening of alkaloids and terpenoids from African medicinal plants", "author": "Gyebi", "doi-asserted-by": "publisher", "journal-title": "J. Biomol. Struct. Dyn.", "key": "B22", "year": "2020" }, { "key": "B23", "volume-title": "MGC Pharmaceutical’s (ASX:MXC) ArtemiC combats COVID-19", "year": "2020" }, { "DOI": "10.1002/path.2067", "article-title": "Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV-infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS", "author": "He", "doi-asserted-by": "publisher", "first-page": "288", "journal-title": "J. Pathol.", "key": "B24", "volume": "210", "year": "2006" }, { "DOI": "10.1007/s00296-009-1218-7", "article-title": "The anti-malaria agent artesunate inhibits expression of vascular endothelial growth factor and hypoxia-inducible factor-1α in human rheumatoid arthritis fibroblast-like synoviocyte", "author": "He", "doi-asserted-by": "publisher", "first-page": "53", "journal-title": "Rheumatol. Int.", "key": "B25", "volume": "31", "year": "2011" }, { "DOI": "10.1016/j.clinthera.2011.04.017", "article-title": "Orally formulated artemisinin in healthy fasting Vietnamese male subjects: a randomized, four-sequence, open-label, pharmacokinetic crossover study", "author": "Hien", "doi-asserted-by": "publisher", "first-page": "644", "journal-title": "Clin. Ther.", "key": "B26", "volume": "33", "year": "2011" }, { "DOI": "10.12659/MSM.915570", "article-title": "Alleviation of inflammatory response of pulmonary fibrosis in acute respiratory distress syndrome by puerarin via transforming growth factor (TGF-β1)", "author": "Hu", "doi-asserted-by": "publisher", "first-page": "6523", "journal-title": "Med. Sci. Monit.", "key": "B27", "volume": "25", "year": "2019" }, { "DOI": "10.3389/fphar.2020.588508", "article-title": "Current prevention of COVID-19: natural products and herbal medicine", "author": "Huang", "doi-asserted-by": "publisher", "first-page": "588508", "journal-title": "Front Pharmacol.", "key": "B28", "volume": "11", "year": "2020" }, { "DOI": "10.1182/blood-2014-02-555953", "article-title": "Postartesunate delayed hemolysis is a predictable event related to the lifesaving effect of artemisinins", "author": "Jauréguiberry", "doi-asserted-by": "publisher", "first-page": "167", "journal-title": "Blood", "key": "B29", "volume": "124", "year": "2014" }, { "DOI": "10.1016/j.phymed.2016.06.004", "article-title": "Artesunate attenuated progression of atherosclerosis lesion formation alone or combined with rosuvastatin through inhibition of pro-inflammatory cytokines and pro-inflammatory chemokines", "author": "Jiang", "doi-asserted-by": "publisher", "first-page": "1259", "journal-title": "Phytomedicine", "key": "B30", "volume": "23", "year": "2016" }, { "DOI": "10.1016/j.pt.2020.10.003", "article-title": "Repurposing antimalarials to tackle the COVID-19 pandemic", "author": "Krishna", "doi-asserted-by": "publisher", "first-page": "8", "journal-title": "Trends Parasitol.", "key": "B31", "volume": "37", "year": "2021" }, { "DOI": "10.1080/07391102.2020.1775704", "article-title": "Withanone and Withaferin-A are predicted to interact with transmembrane protease serine 2 (TMPRSS2) and block entry of SARS-CoV-2 into cells", "author": "Kumar", "doi-asserted-by": "publisher", "journal-title": "J. Biomol. Struct. Dyn.", "key": "B32", "year": "2020" }, { "DOI": "10.1080/09537100600800743", "article-title": "Platelets possess functional TGF-beta receptors and Smad2 protein", "author": "Lev", "doi-asserted-by": "publisher", "first-page": "35", "journal-title": "Platelets", "key": "B33", "volume": "18", "year": "2007" }, { "article-title": "Chapter 6: artemisinin and derivatives: clinical studies", "author": "Li", "first-page": "353", "key": "B34", "volume-title": "Artemisinin-based and other Antimalarials: detailed account of studies by Chinese scientists who discovered and developed them", "year": "2018" }, { "DOI": "10.1016/j.ijantimicag.2020.106216", "article-title": "Safety and efficacy of artemisinin-piperaquine for treatment of COVID-19: an open-label, non-randomised and controlled trial", "author": "Li", "doi-asserted-by": "publisher", "first-page": "106216", "journal-title": "Int. J. Antimicrob. Agents", "key": "B35", "volume": "57", "year": "2021" }, { "DOI": "10.1002/path.2067", "article-title": "SARS coronavirus papain-like protease induces Egr-1-dependent up-regulation of TGF-β1 via ROS/p38 MAPK/STAT3 pathway", "author": "Li", "doi-asserted-by": "publisher", "first-page": "25754", "journal-title": "Sci. Rep.", "key": "B36", "volume": "6", "year": "2016" }, { "DOI": "10.1016/j.intimp.2013.03.011", "article-title": "Evaluation of the immunosuppressive activity of artesunate in vitro and in vivo", "author": "Li", "doi-asserted-by": "publisher", "first-page": "306", "journal-title": "Int. Immunopharmacol.", "key": "B37", "volume": "16", "year": "2013" }, { "DOI": "10.3760/cma.j.cn121430-20200312-00412", "article-title": "[Clinical study of artesunate in the treatment of coronavirus disease 2019]", "author": "Lin", "doi-asserted-by": "publisher", "first-page": "417", "journal-title": "Zhonghua Wei Zhong Bing Ji Jiu Yi Xue", "key": "B38", "volume": "32", "year": "2020" }, { "article-title": "[Effects of artesunate on tumor necrosis factor alpha and chemotactic factors in the serum and the synoviocyte culture supernate of collagen-induced arthritis rats]", "author": "Mo", "first-page": "253", "journal-title": "Zhongguo Zhong Xi Yi Jie He Za Zhi", "key": "B39", "volume": "32", "year": "2012" }, { "DOI": "10.1172/JCI11963", "article-title": "TGF-beta is a critical mediator of acute lung injury", "author": "Pittet", "doi-asserted-by": "publisher", "first-page": "1537", "journal-title": "J. Clin. Invest", "key": "B41", "volume": "107", "year": "2001" }, { "DOI": "10.1186/s12936-020-3120-4", "article-title": "Delayed haemolysis after treatment with intravenous artesunate in patients with severe malaria in India", "author": "Savargaonkar", "doi-asserted-by": "publisher", "first-page": "39", "journal-title": "Malar. J.", "key": "B42", "volume": "19", "year": "2020" }, { "article-title": "In-silico studies of antimalarial-agent artemisinin and derivatives portray more potent binding to Lys353 and Lys31-binding hotspots of SARS-CoV-2 spike protein than hydroxychloroquine: potential repurposing of artenimol for COVID-19", "author": "Sehailia", "journal-title": "ChemRxiv", "key": "B43", "year": "2020" }, { "DOI": "10.1136/bmj.m1610", "article-title": "Therapeutic strategies for COVID-19: new insights into the value of transforming growth factor beta (TGFβ) antagonists such as imatinib and other kinase inhibitors", "author": "Stafford", "doi-asserted-by": "publisher", "first-page": "m1610", "journal-title": "BMJ", "key": "B45", "volume": "369", "year": "2020" }, { "article-title": "Prognostic factors associated with high-risk for fatal ARDS in COVID-19 and potential role for precision Medicines as part of COVID-19 supportive care algorithms", "author": "Uckun", "first-page": "1", "journal-title": "Ann. Pulm. Crit. Care Med.", "key": "B46", "volume": "3", "year": "" }, { "DOI": "10.3389/fphar.2020.00796", "article-title": "Reducing the fatality rate of COVID-19 by applying clinical insights from immuno-oncology and lung transplantation", "author": "Uckun", "doi-asserted-by": "publisher", "first-page": "796", "journal-title": "Front. Pharmacol.", "key": "B47", "volume": "11", "year": "" }, { "DOI": "10.3389/fphar.2020.594321", "article-title": "Rejuveinix shows a favorable clinical safety profile in human subjects and exhibits potent preclinical protective activity in the Lipopolysaccharide-galactosamine Mouse model of acute respiratory distress syndrome and multi-organ failure", "author": "Uckun", "doi-asserted-by": "publisher", "first-page": "594321", "journal-title": "Front. Pharmacol.", "key": "B48", "volume": "11", "year": "" }, { "article-title": "Selectively targeting TGF-β with Trabedersen/OT-101 in treatment of evolving and mild ards in COVID-19", "author": "Uckun", "first-page": "35", "journal-title": "Clin. Invest. (Lond.)", "key": "B49", "volume": "10", "year": "" }, { "article-title": "Medical-scientific rationale for a randomized, placebo-controlled, Phase 2 study of trabedersen/OT-101 in COVID-19 patients with hypoxemic respiratory failure", "author": "Uckun", "first-page": "1", "journal-title": "Ann. Pulm. Crit. Care Med.", "key": "B50", "volume": "3", "year": "2020" }, { "DOI": "10.1021/acschemneuro.0c00601", "article-title": "Could artesunate have a positive effect on the Neurological complications related to infection when it is used in the treatment of COVID-19?", "author": "Uzun", "doi-asserted-by": "publisher", "first-page": "4001", "journal-title": "ACS Chem. Neurosci.", "key": "B51", "volume": "11", "year": "2020" }, { "DOI": "10.1186/s13020-020-00336-8", "article-title": "Artesunate: could be an alternative drug to chloroquine in COVID-19 treatment?", "author": "Uzun", "doi-asserted-by": "publisher", "first-page": "54", "journal-title": "Chin Med.", "key": "B52", "volume": "15", "year": "2020" }, { "DOI": "10.1016/j.virusres.2017.04.008", "article-title": "SARS coronavirus papain-like protease up-regulates the collagen expression through non-Samd TGF-β1 signaling", "author": "Wang", "doi-asserted-by": "publisher", "first-page": "58", "journal-title": "Virus Research", "key": "B53", "volume": "235", "year": "2017" }, { "article-title": "miR-425 reduction causes aberrant proliferation and collagen synthesis through modulating TGF-β/Smad signaling in acute respiratory distress syndrome", "author": "Wang", "first-page": "2604", "journal-title": "Int. J. Clin. Exp. Pathol.", "key": "B54", "volume": "12", "year": "2019" }, { "DOI": "10.3389/fphar.2020.562363", "article-title": "Efficacy and safety of artemisinin-piperaquine for the treatment of uncomplicated malaria: a systematic review", "author": "Wang", "doi-asserted-by": "publisher", "first-page": "562363", "journal-title": "Front Pharmacol.", "key": "B55", "volume": "11", "year": "2020" }, { "first-page": "210", "key": "B56", "volume-title": "Guidelines for the treatment of malaria", "year": "2020" }, { "DOI": "10.1001/jama.2020.19545", "article-title": "Excess deaths from COVID-19 and other causes, March-July 2020", "author": "Woolf", "doi-asserted-by": "publisher", "first-page": "1562", "journal-title": "JAMA", "key": "B57", "volume": "324", "year": "2020" }, { "DOI": "10.1001/jama.2020.24865", "article-title": "COVID-19 as the leading cause of death in the United States", "author": "Woolf", "doi-asserted-by": "publisher", "first-page": "123", "journal-title": "Jama", "key": "B58", "volume": "325", "year": "2021" }, { "DOI": "10.1001/jamainternmed.2020.0994", "article-title": "Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China", "author": "Wu", "doi-asserted-by": "publisher", "first-page": "934", "journal-title": "JAMA Internal Med", "key": "B59", "volume": "180", "year": "2020" }, { "DOI": "10.1093/abbs/gmq101", "article-title": "Therapeutic effect of artemisinin on lupus nephritis mice and its mechanisms", "author": "Wu", "doi-asserted-by": "publisher", "first-page": "916", "journal-title": "Acta Biochim. Biophys. Sin (Shanghai)", "key": "B60", "volume": "42", "year": "2010" }, { "DOI": "10.1093/rheumatology/kem014", "article-title": "Anti-malarial agent artesunate inhibits TNF-alpha-induced production of proinflammatory cytokines via inhibition of NF-kappaB and PI3 kinase/Akt signal pathway in human rheumatoid arthritis fibroblast-like synoviocytes", "author": "Xu", "doi-asserted-by": "publisher", "first-page": "920", "journal-title": "Rheumatology (Oxford)", "key": "B61", "volume": "46", "year": "2007" }, { "DOI": "10.1016/j.ctcp.2020.101165", "article-title": "Traditional Chinese medicine treatment of COVID-19", "author": "Xu", "doi-asserted-by": "publisher", "first-page": "101165", "journal-title": "Complement Ther. Clin. Pract.", "key": "B62", "volume": "39", "year": "2020" }, { "DOI": "10.1126/science.abb2762", "article-title": "Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2", "author": "Yan", "doi-asserted-by": "publisher", "first-page": "1444", "journal-title": "Science", "key": "B63", "volume": "367", "year": "2020" }, { "DOI": "10.1016/j.lfs.2020.117966", "article-title": "Artemisinin attenuates early renal damage on diabetic nephropathy rats through suppressing TGF-β1 regulator and activating the Nrf2 signaling pathway", "author": "Zhang", "doi-asserted-by": "publisher", "first-page": "117966", "journal-title": "Life Sci.", "key": "B64", "volume": "256", "year": "2020" }, { "DOI": "10.1074/jbc.M708033200", "article-title": "Severe acute respiratory syndrome-associated coronavirus nucleocapsid protein interacts with Smad3 and modulates transforming growth factor-beta signalling", "author": "Zhao", "doi-asserted-by": "publisher", "first-page": "3272", "journal-title": "J. Biol. Chem.", "key": "B65", "volume": "283", "year": "2008" }, { "DOI": "10.1016/j.jinf.2020.04.021", "article-title": "Risk factors of critical and mortal COVID-19 cases: a systematic literature review and meta-analysis", "author": "Zheng", "doi-asserted-by": "publisher", "first-page": "e16", "journal-title": "J. Infect.", "key": "B66", "volume": "81", "year": "2020" }, { "DOI": "10.1016/S0140-6736(20)30566-3", "article-title": "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study", "author": "Zhou", "doi-asserted-by": "publisher", "first-page": "1054", "journal-title": "Lancet", "key": "B67", "volume": "395", "year": "2020" }, { "DOI": "10.1172/jci.insight.138999", "article-title": "Neutrophil extracellular traps in COVID-19", "author": "Zuo", "doi-asserted-by": "publisher", "first-page": "e138999", "journal-title": "JCI Insight", "key": "B68", "volume": "5", "year": "2020" } ], "reference-count": 65, "references-count": 65, "relation": {}, "resource": { "primary": { "URL": "https://www.frontiersin.org/articles/10.3389/fphar.2021.649532/full" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Repurposing Anti-Malaria Phytomedicine Artemisinin as a COVID-19 Drug", "type": "journal-article", "update-policy": "https://doi.org/10.3389/crossmark-policy", "volume": "12" }